Self-calibrating optical imaging system

ABSTRACT

The present invention generally relates to optical imaging systems and methods for providing images of two-dimensional and/or three-dimensional distribution of properties of chromophores in various physiological media. More particularly, the present invention relates to optical imaging systems, optical probes thereof, and methods therefor utilizing self-calibration of their output signals. A typical self-calibrating optical imaging system includes at least one wave source, at least one wave detector, a signal analyzer, a signal processor, and an image processor. The signal analyzer receives, from the wave detector, an output signal representative of the distribution of the chromophores or their properties in, target areas of the medium. The signal analyzer analyzes amplitudes of the output signal and selects multiple points of the output signal having substantially similar amplitudes. The signal processor calculates a baseline corresponding to a representative amplitude of the similar amplitudes and provides a self-calibrated output signal. The image processor constructs the images of the distribution of the chromophores or their properties from the self-calibrated first output signals.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of the filing date of U.S.Provisional Patent Application bearing Serial No. 60/223,074, entitled“A Self-Calibrated Optical Scanner for Diffuse Optical Imaging” andfiled on Aug. 4, 2000.

FIELD OF THE INVENTION

[0002] The present invention generally relates to optical imagingsystems, optical probes thereof, and methods thereof for providingimages of spatial or temporal distribution of chromophores or propertiesthereof in a physiological medium. In particular, the present inventionrelates to a self-calibrating optical imaging system. The presentinvention is applicable to optical imaging systems whose operation isbased on wave equations such as the Beer-Lambert equation, modifiedBeer-Lambert equation, photon diffusion equation, and their equivalents.

BACKGROUND OF THE INVENTION

[0003] Near-infrared spectroscopy has been used to measure variousphysiological properties in animal and human subjects. The basicprinciple underlying the near-infrared spectroscopy is that aphysiological medium such as tissues and cells includes a variety oflight-absorbing and light-scattering chromophores which can interactwith electromagnetic waves transmitted thereto and travelingtherethrough. For example, human tissues include numerous chromophoresamong which deoxygenated and oxygenated hemoglobins are the mostdominant chromophores in the spectrum range of 600 nm to 900 nm.Therefore, the near-infrared spectroscope has been applied to measureoxygen levels in the physiological medium in terms of tissue hemoglobinoxygen saturation (or simply “oxygen saturation”hereinafter). Technicalbackground for the near-infrared spectroscopy and diffuse opticalimaging has been discussed in, e.g., Neuman, M. R., “Pulse Oximetry:Physical Principles, Technical Realization and Present Limitations,”Adv. Exp. Med. Biol., vol. 220, p.135-144, 1987, and Severinghaus, J.W., “History and Recent Developments in Pulse Oximetry,” Scan. J Clin.and Lab. Investigations, vol. 53, p.105-111, 1993.

[0004] Various techniques have been developed for the near-infraredspectroscopy, including time-resolved spectroscopy (TRS), phasemodulation spectroscopy (PMS), and continuous wave spectroscopy (CWS).In a homogeneous, semi-infinite model, the TRS and PMS are generallyused to solve the photon diffusion equation, to obtain the spectra ofabsorption coefficients and reduced scattering coefficients of thephysiological medium, and to estimate concentrations of the oxygenatedand deoxygenated hemoglobins and oxygen saturation. The CWS hasgenerally been used to solve the modified Beer-Lambert equation and tocalculate changes in the concentrations of the oxygenated as well asdeoxygenated hemoglobin.

[0005] Despite their capability of providing hemoglobin concentrationsas well as the oxygen saturation, the major disadvantage of the TRS andPMS is that the equipment has to be bulky and, therefore, expensive. TheCWS may be manufactured at a lower cost but is generally limited in itsutility, for it can estimate only the changes in the hemoglobinconcentrations but not the absolute values thereof. Accordingly, the CWScannot provide the oxygen saturation. The prior art technology alsorequires a priori calibration of optical probes before their clinicalapplication by, e.g., measuring a baseline in a reference medium or in ahomogeneous portion of the medium. Furthermore, all prior art technologyemploys complicated image reconstruction algorithms to generate imagesof two-dimensional and/or three-dimensional distribution of thechromophore properties.

[0006] Therefore, there exist needs for an efficient, compact, andrelatively cheap optical imaging system which self-calibrates itselfwithout relying on external measurement or data and which provides two-and/or three-dimensional images on a substantially real time basis.

SUMMARY OF THE INVENTION

[0007] The present invention generally relates to optical imagingsystems, optical probes, signal and/or image processing algorithms, andmethods thereof for providing two-or three-dimensional images of spatialor temporal distribution of chromophores or their properties in aphysiological medium. More particularly, the present invention relatesto novel self-calibrating optical imaging systems and methods thereof.

[0008] In one aspect of the present invention, an optical imaging systemis provided to generate images of distribution of chromophores or theirproperties in target areas of various physiological media. The opticalimaging system includes at least one wave source arranged to irradiateelectromagnetic waves into the target areas of the medium and at leastone wave detector arranged to detect electromagnetic waves from thetarget areas and to generate output signal in response thereto. Theoptical imaging system further includes an optical probe, a signalanalyzer, and a signal processor. The optical probe typically includesthe wave source and wave detector. The signal analyzer receives, fromthe wave detector, a first output signal which is representative of thedistribution of the chromophores or their properties in a first targetarea of the medium. The signal analyzer analyzes an amplitude of eachpoint of the first output signal and selects one or more points orportions of the first output signal having substantially similar firstamplitudes. The signal processor calculates a first baseline from thefirst output signal, where the first baseline generally corresponds to arepresentative amplitude of the first amplitudes of the foregoing pointsor portions, and provides a self-calibrated first output signal bymanipulating the first output signal and first baseline thereof.Therefore, the optical imaging system provides the self-calibratedoutput signal representing a spatial distribution and/or temporalvariation of the chromophores or their properties in the first targetarea.

[0009] The foregoing optical imaging systems, probes, algorithms, andmethods (collectively referred to as “optical imaging system” or“optical probe” hereinafter) of the present invention provide numerousadvantages. Contrary to the prior art optical imaging devices thatrequire a priori measurement and estimation of an output signal baselinein a reference medium (or area) before their clinical applications, theoptical imaging system of the present invention allows a user todirectly scan a target area, to obtain the output signal, and tosimultaneously obtain the baseline of the output signal. Accordingly,the optical imaging system of the present invention obviates the needfor a prior estimation of the baseline in other reference media (orareas). In addition, because the foregoing optical imaging system canestimate the baseline and the output signals from the same target area,it does not suffer from noises or errors attributed to different opticalcharacteristics between the reference and target areas. Furthermore, dueto simpler algorithms for estimating the baseline, the optical imagingsystem of the present invention allows real-time calibration of theoutput signals and, therefore, contributes to the real-time constructionof images of the distribution of the chromophore or its properties.

[0010] Embodiments of this aspect of the present invention includes oneor more of the following features.

[0011] The optical probe includes a scanning area which is almost equalto or as large as at least a substantial portion of the first targetarea of the medium. Multiple wave sources and detectors are disposed inthe scanning area so that the chromophore properties in the first targetarea can be measured by a single measurement in the first target area.In the alternative, the optical probe may include a scanning area whichmay be only a small region of the first target area. In this embodiment,the optical imaging system includes an actuator member arranged to moveat least one of the wave source and wave detector so that at least asubstantial portion of the first target area can be scanned thereby.Accordingly, the wave detector can generate multiple first outputsignals while the optical probe or its main housing is positioned andmaintained stationary in the first target area. This embodiment allowsconstruction of compact optical probes with a minimal number of the wavesources and/or detectors implemented thereto. In addition, such opticalprobes can minimize the noises or errors attributed to idiosyncraticcomponent variations among system components.

[0012] The foregoing optical imaging system may also include an imageprocessor which constructs the images of the distribution of thechromophores or properties thereof from the self-calibrated first outputsignals, preferably on a substantially real-time basis. The signalanalyzer and processor may also operate on a substantially real-timebasis and provide the self-calibrated first output signal withoutdisplacing the optical probe from the first target area. The opticalimaging system may further include a memory for storing the first outputsignal, first baseline, self-calibrated first output signal, and othersignals or data.

[0013] The signal analyzer may include a threshold unit for obtaining athreshold amplitude, a comparison unit for comparing the amplitudes ofthe points or portions of the first output signal with the thresholdamplitude, and a selection unit for identifying multiple selected pointsor portions of the first output signal. The threshold unit may receivethe threshold amplitude from a user. Alternatively, the threshold unitmay calculate a reference amplitude based on the first output signal andthen calculate the threshold amplitude from the reference amplitude,where the reference amplitude may be, e.g., a local maximum or minimumof the first output signal measured in the first target area, an averageof at least one or entire portion of the first output signal, a globalmaximum or minimum of multiple output signals measured in multipletarget areas over the medium, and their combinations. The thresholdamplitude may be calculated as a product of the reference amplitude anda pre-determined factor which may be encoded therein or may be providedby the operator. Therefore, depending on the mode of selecting thethreshold amplitude, the first amplitudes of the selected points orportions may be either greater or less than the threshold amplitude.

[0014] Alternatively, the signal analyzer may include a threshold unitfor obtaining a threshold range of amplitudes, a comparison unit forcomparing the amplitudes of the points or portions of the first outputsignal with the threshold range, and a selection unit arranged toidentify those selected points or portions of the first output signal.Accordingly, the first amplitudes of the selected points may fall withinor outside the threshold range.

[0015] The signal analyzer may also include a filter unit arranged toimprove signal-to-noise ratio of the first output signals. The filterunit may include an algorithm arranged to arithmetically, geometrically,weight- or ensemble-averaging multiple first output signals. The filterunit may also include a low pass filter for removing high frequencynoises from the first output signal.

[0016] The signal processor may include an averaging unit forcalculating the first baseline by arithmetically, geometrically, weight-or ensemble-averaging the substantially similar first amplitudes of theforegoing points or portions. The signal processor may also include acalibration unit for obtaining the self-calibrated first output signalby normalizing the first output signal by its first baseline, where theself-calibrated first output signal may be defined as a ratio of thefirst output signal to the first baseline or a ratio of a differencebetween the first output signal and first baseline to the firstbaseline.

[0017] The signal analyzer may also include a control unit which storesmultiple baselines measured in multiple target areas and compares one oreach baseline from the others thereof. The control unit may calculate anaverage of such multiple baselines. The control unit may be arrangedsend a signal or alarm to the operator when at least one of thebaselines is at least substantially different from at least one of theothers.

[0018] In another aspect of the invention, an optical imaging system isprovided to generate images of distribution of chromophores or theirproperties in target areas of a physiological medium. The opticalimaging system includes at least one of the foregoing wave sources andat least one of the foregoing wave detectors. The optical imaging systemalso includes a signal analyzer, signal processor, and image processor.The signal analyzer receives, from the wave detector, a first outputsignal representative of the foregoing distribution in a first targetarea of the medium, analyzes amplitudes of the first output signal, andselects multiple points or portions of the first output signal havingsubstantially similar first amplitudes. The signal processor calculates,from the first output signal, a first baseline which corresponds to arepresentative value of the first amplitudes, and provides aself-calibrated first output signal by manipulating both of the firstoutput signal and its first baseline. The image processor constructs theimages of the foregoing distribution from the self-calibrated firstoutput signals.

[0019] In yet another aspect of the present invention, an opticalimaging system is provided to generate images of the foregoingdistribution in target areas of a physiological medium. The opticalimaging system includes at least one of the foregoing wave sources andat least one of the foregoing wave detectors along with a movablemember, actuator member, signal analyzer, signal processor, and imageprocessor. The movable member includes at least one of the wave sourceand detector, and the actuator member generates at least one movement ofthe movable member. The signal analyzer receives, from the wavedetector, a first output signal representing the foregoing distributionin a first target area of the medium, analyzes an amplitude of eachpoint of the first output signal, and selects multiple points orportions of the first output signal having substantially similar firstamplitudes. The signal processor calculates, from the first outputsignal, a first baseline which corresponds to a representative amplitudeof the first amplitudes, and provides a self-calibrated first outputsignal by manipulating the first output signal and its first baseline.The image processor then constructs the images of the foregoingdistribution from the self-calibrated first output signals.

[0020] In a further aspect of the present invention, a method isprovided to obtain a calibrated output signal from an optical imagingsystem which includes an optical probe with the foregoing wave sourceand detector. The method includes the steps of positioning the opticalprobe on a first target area of said medium, generating a first outputsignal without displacing the optical probe from the first target area,identifying at least one first portion of the first output signal havingsubstantially similar first amplitudes, and obtaining a first baselineof the first output signal from a representative value of the foregoingfirst portion having the first amplitudes.

[0021] Embodiments of this aspect of the present invention includes oneor more of the following features.

[0022] The method may also include the step of normalizing the firstoutput signal by the first baseline to provide a self-calibrated firstoutput signal. In addition, the method may include the step of reducingnoise from the first output signal prior to performing the foregoingidentifying and obtaining steps. The reducing step may include the stepof, e.g., arithmetically, geometrically, weight- or ensemble-averagingmultiple first output signals or the step of processing at least aportion of the first output signal through a low-pass filter.

[0023] The generating step may include the step of providing movement ofat least one of the wave source and detector over the different regionsof the first target area, while generating the first output signalduring such movement.

[0024] The identifying step may include the step of selecting athreshold amplitude and identifying the first portion of the firstoutput signal having the amplitudes greater or less than the thresholdamplitude. The identifying step may alternatively include the steps ofselecting at least one threshold range and identifying the first portionwhich has the amplitudes within or outside the threshold range. Suchselecting steps may be manually selecting the threshold amplitude and/orrange, or identifying a reference amplitude or range and providing thethreshold amplitude and/or range therefrom. The reference amplitude maybe selected as a local maximum or minimum of the first output signalmeasured in the first target area, an average of one or entire portionof the first output signal, a global maximum or minimum of multipleoutput signals measured in multiple target areas over the medium, and acombination thereof.

[0025] The obtaining step may include one of arithmetically,geometrically, and/or weight-averaging the first amplitudes of the firstportion of the first output signal.

[0026] The method may further include the steps of moving the opticalprobe to a second target area of the medium, generating a second outputsignal from the second target area, and normalizing the second outputsignal by the first baseline from the first-target area to provide aself-calibrated second output signal. Such moving and generating stepsmay also be repeated in other target areas of the medium. Alternatively,the method may include the steps of moving the optical probe to a secondtarget area of the medium, generating a second output signal from thesecond target area, identifying, from the second output signal, at leastone second portion having substantially similar second amplitudes, andobtaining a second baseline of the second output signal corresponding toa representative amplitude of the second amplitudes. A compositebaseline may be obtained by averaging the first and second baselines byarithmetically, geometrically, weight-, and/or ensemble-averaging suchbaselines or by manually selecting one of the baselines as the compositebaseline.

[0027] In yet another aspect of the invention, yet another method isprovided to obtain a calibrated output signal from an optical imagingsystem including the foregoing optical probe with the foregoing wavesource and detector. The method includes the steps of positioning theoptical probe on a first target area of a physiological medium with anormal region and an abnormal region, generating a first output signalwithout displacing the optical probe from the first target area,identifying from the first output signal at least one first portion ofthe first output signal attributed to the normal region of the targetarea, and obtaining a first baseline of the first output signal from arepresentative value of the first portion of the first output signal.

[0028] Embodiments of this aspect of the present invention includes oneor more of the following features.

[0029] The method may also include the step of normalizing the firstoutput signal by the first baseline to provide a self-calibrated firstoutput signal. The first portion of the first output signal may have asubstantially flat profile and/or such first portion may havesubstantially similar first amplitudes.

[0030] In a further aspect of the present invention, yet another methodis provided for calibrating an optical imaging system which includes theforegoing optical probe with the foregoing wave source and detector.Such method includes the steps of positioning the optical probe on afirst target area of a physiological medium, generating a first outputsignal without displacing the optical probe from the first target area,identifying from the first output signal at least one first portionwhich has substantially similar first amplitudes before displacing theoptical probe from the first target area, and obtaining a first baselineof the first output signal which is a representative value of thesimilar first amplitudes before displacing the optical probe from thefirst target area.

[0031] Embodiments of this aspect of the present invention includes oneor more of the following features.

[0032] The method may include the step of normalizing the first outputsignal by the first baseline to provide a self-calibrated first outputsignal on a substantially real time basis. The method may also includethe step of generating images of the first output signal, images of theself-calibrated first output signal, images derived from the firstoutput signal, and images derived from the self-calibrated first outputsignal.

[0033] Each of the foregoing optical imaging systems and methods of thepresent invention may incorporate analytical and/or numerical solutionschemes disclosed in the commonly assigned co-pending U.S.non-provisional patent application bearing Ser. No. 09/664,972, entitled“A system and Method for Absolute Oxygen Saturation” by Xuefeng Cheng,Xiaorong Xu, Shuoming Zhou, and Ming Wang on Sep. 18, 2000 which isincorporated herein by reference in its entirety (referred to as “the'972 application”hereinafter). Therefore, the absolute values ofconcentration of oxygenated hemoglobin, [HbO], concentration ofdeoxygenated hemoglobin, [Hb], oxygen saturation, [SO₂], and temporalchanges in blood volume may be obtained by any of the solution schemesof the co-pending '972 application, and images thereof may be providedto allow physicians to make direct diagnosis of the target area of themedium based on the “absolute” and/or “relative” values of thechromophore properties in the physiological media. In addition,operational characteristics of the optical imaging systems of thepresent invention are generally not affected by the precise number ofthe wave sources and/or detectors and by geometric arrangementtherebetween.

[0034] As used herein, a “chromophore” means any substance in aphysiological medium which can interact with electromagnetic wavestransmitting therethrough. Such chromophore may include solvents of amedium, solutes dissolved in the medium, and/or other substancesincluded in the medium. Specific examples of such chromophores mayinclude, but not limited to, cytochromes, enzymes, hormones, proteins,cholesterols, lipids, apoproteins, chemotransmitters, neurotransmitters,carbohydrates, cytosomes, blood cells, cytosols, water, oxygenatedhemoglobin, deoxygenated hemoglobin, and other materials present in theanimal or human cells, tissues or body fluid. The “chromophore” may alsoinclude any extra-cellular substance which may be injected into themedium for therapeutic or imaging purposes and which may interact withelectromagnetic waves. Typical examples of such chromophores mayinclude, but not limited to, dyes, contrast agents, and/or otherimage-enhancing agents, each of which exhibits optical interaction withelectromagnetic waves having wavelengths in a specific range.

[0035] “Hemoglobins” are oxygenated hemoglobin (i.e., HbO) and/ordeoxygenated hemoglobin (i.e., Hb). Unless otherwise specified,“hemoglobins” refer to both oxygenated and deoxygenated hemoglobins.“Total hemoglobin” means the sum of the oxygenated and deoxygenatedhemoglobins.

[0036] “Electromagnetic waves” as used herein may include acoustic orsound waves, near-infrared rays, infrared rays, visible light rays,ultraviolet rays, lasers, and/or photons.

[0037] “Property” of the chromophore refers to intensive propertythereof such as concentration of the chromophore, a sum ofconcentrations thereof, a ratio thereof, and the like. “Property” mayalso refer to extensive property such as, e.g., volume, mass, weight,volumetric flow rate, and mass flow rate of the chromophore.

[0038] The term “value” is an absolute or relative value whichrepresents spatial or temporal changes in the property of thechromophores (or hemoglobins).

[0039] “Distribution” refers to two-dimensional or three-dimensionaldistribution of the chromophores or their properties. The “distribution”may be measured or estimated in a spatial and/or temporal domain.

[0040] Unless otherwise defined, all technical and scientific terms usedherein have the same meaning as commonly understood and/or used by oneof ordinary skill in the art to which this invention belongs. Althoughmethods and materials similar or equivalent to those described hereincan be applied and/or used in the practice of or testing the presentinvention, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present application, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

[0041] Other features and advantages of the invention will be apparentfrom the following detailed description and from the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0042]FIGS. 1A to 1D are exemplary arrangements of wave sources anddetectors of an optical imaging system according to the presentinvention;

[0043]FIGS. 2A and 2B are exemplary output signals generated by wavedetectors according to the present invention;

[0044]FIG. 3 is a schematic diagram of a typical self-calibratingoptical imaging system according to the present invention;

[0045]FIGS. 4A to 4C are further exemplary output signals generated bywave detectors according to the present invention;

[0046]FIG. 5 is a schematic view of another exemplary optical imagingsystem according to the present invention;

[0047]FIGS. 6A and 6B are images of changes in blood volume in bothnormal and abnormal breast tissues, respectively, measured by theoptical imaging system of FIG. 5 according to the present invention; and

[0048]FIGS. 7A and 7B are images of oxygen saturation in normal andabnormal breast tissues, respectively, measured by the optical imagingsystem of FIG. 5 according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0049] The following description provides various optical imagingsystems arranged to provide images of two- and/or three-dimensionalspatial and/or temporal distribution of properties of chromophores in aphysiological medium. More particularly, the following descriptionprovides preferred aspects and embodiments of optical imaging systems,optical probes thereof, and methods thereof for calibrating their outputsignals.

[0050]FIGS. 1A through 1D are exemplary arrangements of wave sources andwave detectors of an optical imaging system according to the presentinvention. The exemplary optical imaging system typically includes anoptical probe having a scanning surface 120 a-120 d on which multiplewave sources 122 and detectors 124 (both collectively referred to as“sensors” hereinafter) are disposed.

[0051] In general, each pair of wave source 122 and detector 124 forms ascanning element representing a functional unit from which wave source122 emits electromagnetic waves into a target area of a medium and wavedetector 124 detects electromagnetic waves interacted with and emanatingfrom the target area of the medium. Wave detector 124 generates acorresponding output value signal or data point signal representing anamount of the electromagnetic waves detected thereby across the scanningelement. A group of wave sources 122 and detectors 124 or a group ofscanning elements also defines a scanning unit 125 which generally formsan effective scanning area of the optical probe of the invention. As aresult, the group of sensors 122, 124 generates an output signalcorresponding to a collection of multiple output value signals or datapoint signals each of which is generated in its corresponding scanningelement. Configuration of scanning unit 125 and its scanning area ispredominantly determined by geometric arrangements of a sensor assemblyand/or source-detector arrangement such as, e.g., the number of wavesources 122 and detectors 124, geometric arrangement therebetween,grouping of wave sources 122 and detectors 124 for the scanning elementsand for the scanning units, irradiation capacity or emission power ofwave source 122, detection sensitivity of wave detector 124, and thelike. For example, in the embodiment of FIG. 1A, two wave detectors 124are interposed between two wave sources 122, preferably at equaldistances. Therefore, sensors 122, 124 define, on scanning area 120 a, a“linear” scanning unit 125 a that is substantially elongated along alongitudinal axis 127 thereof. In the embodiment of FIG. 1B, a row ofwave sources 122 is disposed directly above a second row of wavedetectors 124 in a substantially parallel fashion, and defines asubstantially rectangular or square “areal” scanning unit 125 b onscanning area 120 b. The embodiment of FIG. 1C includes four parallelrows of sensors in each of which two wave detectors 124 (or sources 122)are interposed between two wave sources 122 (or detectors 124). Sensors122, 124 form a scanning unit 125 c substantially rectangular or squarebut substantially wider than one 125 a of FIG. 1A and larger than one125 b of FIG. 1B. It is noted that, depending on the grouping of thesensors 122, 124, scanning unit 125 c of optical probe 120 c can definemultiple scanning units 125 a, 125 b which have differentconfigurations. To the contrary, the embodiment in FIG. 1D includes wavedetectors 124 disposed around wave sources 122 to define a substantiallycircular scanning unit 125 d on its circular scanning area 120 d. It isalso appreciated that wave sources 122 and detectors 124 of circularscanning unit 125 d may be grouped to define foregoing “linear” scanningunits 125 a as well as “aerial” scanning units 125 b.

[0052] The wave sources of the present invention are generally arrangedto form optical coupling with the medium and to irradiateelectromagnetic waves thereinto. Any wave sources may be employed in theoptical imaging systems or optical probes thereof to irradiateelectromagnetic waves having pre-selected wavelengths, e.g., in theranges from 100 nm to 5,000 nm, from 300 nm to 3,000 nm or, inparticular, in the “near-infrared” range from 500 nm to 2,500 nm. Aswill be described below, however, typical wave sources are arranged toirradiate near-infrared electromagnetic waves having wavelengths ofabout 690 nm or about 830 nm. The wave sources may also irradiateelectromagnetic waves having different wave characteristics such asdifferent wavelengths, phase angles, frequencies, amplitudes, harmonics,etc. Alternatively, the wave sources may irradiate electromagnetic wavesin which identical, similar or different signal waves are superposed oncarrier waves with similar or mutually distinguishable wavelengths,frequencies, phase angles, amplitudes or harmonics. In the embodimentsof FIGS. 1A to 1D, each wave source 122 is arranged to irradiateelectromagnetic waves having two different wave lengths, e.g., about 660nm to 720 nm, e.g., 690 nm, and about 810 nm to 850 nm, e.g., 830 nm.

[0053] Similarly, the foregoing wave detector is preferably arranged todetect the aforementioned electromagnetic waves and to generate theoutput signal in response thereto. Any wave detectors may be used in theoptical imaging systems or optical probes thereof as long as they haveappropriate detection sensitivity to the electromagnetic waves havingwavelengths in the foregoing ranges. The wave detector may also beconstructed to detect electromagnetic waves which may have any of theforegoing wave characteristics. The wave detector may also detectmultiple sets of electromagnetic waves irradiated by multiple wavesources and generate multiple output signals accordingly.

[0054]FIGS. 2A and 2B are exemplary output signals generated by theforegoing wave detector(s) according to the present invention. In thefigures, the abscissa is an axial distance along an optical probe of theoptical imaging system or that along the physiological medium, while theordinate represents the amplitude of the output signal measured by thewave detector in the target areas of the medium. Each output signal isgenerally comprised of multiple output value signals or data pointsignals each corresponding to electromagnetic waves detected by the wavedetector of each scanning element of each scanning unit. Forillustrative purposes, the target area located at the far-left end ofthe medium (i.e., adjacent the origin of the figures) is designated asthe “first” target area, while the target area at the far right end ofthe medium as the “last” target area. As illustrated in FIG. 2A,exemplary output signal 150 exhibits relatively flat profile in thefirst portion or region 152 a (i.e., from the first to the i-th targetarea) and in the second portion or region 152 b (i.e., from the j-th tothe M-th, last target area). In between flat regions 152 a, 152 b liesan upright bell-shaped portion 154 a (i.e., from the (i+1)-th to the(j-1)-th target area) where the amplitudes of output signal 150 varywith respect to the axial position. Output signal 150 of FIG. 2B has acontour similar to that of FIG. 2A, except that an inverted bell-shapedportion 154 b (i.e., from the (i+1)-th to the (j-1)-th target area) isinterposed between two flat portions 152 a, 152 b.

[0055] In a medium composed of a majority of normal tissues, flatportions 152 a, 152 b of output signal 150 generally correspond tonormal cells or tissues and, therefore, constitute a background outputsignal level for the medium (referred to as a “baseline” of the outputsignal hereinafter). To the contrary, upright and inverted bell-shapedportions 154 a, 154 b generally represent abnormal tissues or cells(e.g., tumor tissues, malignant or benign carcinoma such as fibercarcinoma, fluid sacks, and the like) at various development stages.Curved portions 154 a, 154 b may also represent normal anatomic tissuesor cells (e.g., blood vessels, connective tissues, etc.) which haveoptical properties different from those of the background tissues orcells.

[0056] In estimating concentrations of oxygenated and deoxygenatedhemoglobins, oxygen saturation, blood volume, and other chromophoreproperties, there exist needs for calibrating the output signalsgenerated by the wave detectors for initializing the sensors and/or foraccounting for the idiosyncratic differences in various scanningelements of the target areas of the medium. Furthermore, signalprocessing algorithms used in the optical imaging system generallyrequire not the output signals themselves but ratios of the outputsignals (e.g., optical density) where the output signals are normalizedor calibrated by a reference output signal. Accordingly, one aspect ofthe present invention is to provide an optical imaging system capable ofperforming self-calibration of the output signals based on theproperties of the output signals themselves.

[0057]FIG. 3 shows a schematic diagram of an exemplary self-calibratingoptical imaging system according to the present invention for generatingimages of distribution of chromophores or their properties in the targetarea of a physiological medium. An optical imaging system 100 typicallyincludes at least one wave source 122, at least one wave detector 124,and power source 102. Optical imaging system 100 further includeshardware (circuitry, processors or integrated circuits) or software suchas a signal analyzer 160, signal processor 170, and image processor 180,each of which may be operationally coupled to the others and each ofwhich may include one or more functional units.

[0058] Signal analyzer 160 operationally couples with one or moresensors 122, 124 so that the signal analyzer can monitor various inputand output signals which are required for generating the images of thedistribution of the chromophore (or its properties) in the target areaof the medium. For example, signal analyzer 160 includes one or morereceiving units which operationally couple with wave source 122 andmonitor the characteristics of electromagnetic waves irradiated thereby.Each of the receiving units also communicates with wave detector 124 andreceives therefrom a first output signal which represents thedistribution of the chromophore (or its properties) in a first targetarea of the medium. The receiving unit may also be arranged to receiveexternal data, operational parameters, and/or other command or controlsignals supplied by an operator or encoded therein.

[0059] Signal analyzer 160 may include other functional units such as asampling unit, threshold unit, comparison unit, selection unit, etc. Thesampling unit receives the foregoing input or output signals or datafrom the receiving unit and samples the signals at a pre-selectedfrequency in an analog and/or digital mode. The threshold unitoperationally couples with the sampling unit and determines a thresholdor cut-off amplitude (or range) which is to be used by the subsequentfunctional units such as the comparison and selection units. Thethreshold amplitude or range may be pre-selected and encoded in thethreshold unit. The threshold amplitude (or its range) may be manuallysupplied to the threshold unit by the operator. In the alternative, thethreshold amplitude (or its range) may be calculated from the firstoutput signal itself. For example, the threshold unit may identify oneor more local maximum or minimum amplitudes of the first output signalmeasured in the first target area, to calculate an average amplitude ofat least one or entire portion of such first output signal, to locate aglobal maximum or minimum amplitude from multiple output signals to bemeasured in multiple target areas over the medium. After designatingsuch amplitude as a reference amplitude, the threshold unit maycalculate the threshold amplitude, e.g., by multiplying the referenceamplitude with a pre-selected factor which is generally less than 1.0,by adding thereto or subtracting therefrom another pre-selected factor,by employing a function which yields the threshold amplitude bysubstituting the foregoing maximum or minimum amplitudes into thefunction, and the like. The threshold unit may alternatively be encodedwith or may include a pre-selected threshold range, receive the rangefrom the operator, or calculate the range based on the foregoing maximumor minimum amplitudes. The comparison unit generally communicates withthe threshold unit, receives the threshold amplitude or range therefrom,and compares it with the amplitudes of the first output signal. Theselection unit receives the results from the comparison unit and selectsmultiple points or portions of the first output signal having identicalor substantially similar amplitudes. More particularly, when thethreshold unit is arranged to provide the threshold amplitude, theselection unit selects the points or portions of the first output signalhaving amplitudes greater (or less) than the threshold amplitude.However, when the threshold unit provides the threshold range, theselection unit selects multiple points or portions of the first outputsignal falling within (or outside) the threshold range.

[0060] Signal processor 170 operationally couples with signal analyzer160 and is arranged to “self-calibrate” the first output signal by thefirst baseline which is obtained from the first output signal itself.Similar to signal analyzer 160, signal processor 170 also includesfunctional units such as an averaging unit and calibration unit. Theaveraging unit averages the similar amplitudes of the points or portionsof the first output signal selected by the selection unit and designatessuch average as the baseline of the first output signal. For example,the averaging unit may arithmetically, geometrically, weight- orensemble-average the similar amplitudes of the foregoing points orportions. Once the first baseline is obtained from the first outputsignal, the calibration unit normalizes or non-dimensionalizes the firstoutput signal by the first baseline, and provides a self-calibratedfirst output signal which may be, e.g., a ratio of their amplitudes(i.e., the ratio of the first output signal to its first baseline toyield the optical density signals) or a ratio of their amplitudedifferences to the first baseline.

[0061] Image processor 180 operationally couples with signal processor170 and is arranged to construct the images of the chromophore (or itsproperties) based on the self-calibrated first output signal. Typicalimage processor 180 includes an algorithm unit and an imagingconstruction unit. The algorithm unit is encoded with or includes atleast one solution scheme for solving a set of wave equations applied towave source(s) 122 and detector(s) 124 arranged according to apre-selected geometric arrangement. By supplying the algorithm unit withthe self-calibrated first output signal along with other requisiteinitial and/or boundary conditions, the algorithm unit solves the set ofthe wave equations and provides a set of solutions representing at leastone of concentrations of oxygenated or deoxygenated hemoglobins, oxygensaturation, blood volume, other intensive or extensive properties of thechromophores, and the like . The image construction unit then receivesthe set of solution signals and constructs the images of the spatialdistribution of the foregoing properties of the chromophores. Ifpreferred, the image construction unit may be arranged to construct theimages regarding the distribution pattern of the first output signal,those of the self-calibrated first output signal itself, and the like.

[0062] The foregoing optical imaging systems and methods of the presentinvention offer several benefits over the prior art optical imagingdevices. One of the most serious problems of the prior art devices liesin the fact that their optical probes or sensors require a prioriestimation of the baseline of their output signals. For example, theprobes or sensors are positioned in a reference medium (e.g., a phantom)or in a reference area of the subject, output signals are generated bythe wave detectors, and baselines are estimated based on the opticalproperty of the reference medium or area. The probes or sensors are thenmoved and placed on the target area of the subject to be scannedthereby. It is well known in the field that such calibration methodconstitutes a major source of error in the resulting signals due topossible inherent differences in optical properties between the targetarea and reference medium or area. In addition, repositioning the probesor sensors from the reference area to the target area frequently resultsin inconsistent optical coupling between the sensors and target area andbetween the sensors and reference medium (or area), thereby introducingadditional noises thereto. The optical imaging system of the presentinvention, however, allows the operator to obtain the first outputsignal and first baseline thereof from the same target area withoutmoving and/or repositioning the optical probes or sensors from the firsttarget area. Because the foregoing optical imaging system obtains thebaseline from the same target area of the same medium under theidentical optical coupling (therefore referred to as“self-calibration”), the optical imaging system of the present inventionobviates the need for such reference measurement and, thus, eliminatesthe error associated with the inconsistent optical coupling. Inaddition, because the foregoing optical imaging systems can estimate thefirst output signal and its baseline from the same target area, suchoptical imaging system provides more accurate and reliable results.Furthermore, due to the simple data processing algorithms for estimatingsuch baseline, the foregoing optical imaging system allows constructionof the images of the chromophore properties on a substantially real-timebasis.

[0063] The foregoing optical imaging systems and methods thereof may bemodified in various aspects without departing from the scope of thepresent invention.

[0064] First of all, it is appreciated that the exact number of the wavesources and detectors and geometric arrangements therebetween are notcritical in realizing the present invention described herein.Accordingly, virtually any number of wave sources and wave detectors maybe implemented into the optical probe of the optical imaging system inany geometric arrangements. The self-calibrating feature of the presentinvention then applies to each scanning element formed by each pair ofthe wave source and detector which may irradiate multiple sets ofelectromagnetic waves having, e.g., different wave characteristics,identical or different signal waves superposed on different or identicalcarrier waves, and the like. The wave sources may also be arranged toirradiate such electromagnetic waves continuously, periodically orintermittently.

[0065] As discussed in the co-pending '972 application, it is generallypreferred, however, that the wave sources and detectors be arrangedaccording to a few semi-empirical design rules which are expected toenhance accuracy, reliability, and/or reproducibility of the signalbaselines as well as the estimated absolute values of the chromophoreproperties. Such exemplary design rules are: (1) the scanning unitpreferably includes at least two wave sources and at least two wavedetectors; and (2) the distances between any wave source and wavedetector within a scanning unit do not exceed a threshold sensitivityrange of the wave detector which may range from, e.g., several to 10 cmor, in particular, about 5 cm for most human and/or animal tissues.Furthermore, the wave sources and detectors are preferably arranged todefine the scanning units having continuous scanning area throughout theentire region thereof so that a single measurement by the scanning unitcan generate the output signal covering the entire scanning area. Forthis purpose, the wave sources and detectors may be spaced at distancesno greater than a threshold distance thereof. Selection of the optimalspacing between the wave sources and detectors is generally a matter ofchoice of one of ordinary skill in the art and such spacing isdetermined by many factors including, e.g., optical properties of themedium (e.g., absorption coefficient, scattering coefficient, and thelike), irradiation or emission capacity of the wave sources, detectionsensitivity of the wave detectors, configuration of the scanningelements and units, number of the wave sources and/or detectors in theoptical probe, geometric arrangement between the wave sources anddetectors, grouping of the wave sources and detectors in each of thescanning elements and each of the scanning units, and so on.

[0066] The optical imaging system may include a filter unit to improve asignal-to-noise ratio of the output signals as well as that ofsubsequent signals including the baselines and self-calibrated outputsignals. Accordingly, the filter unit is preferably arranged to treatthe output signals before they are processed by the signal analyzer andprocessor. When a single output signal is obtained for each target area(or medium), the filter unit preferably includes a low pass filter whichmay remove high-frequency noises from the output signals.

[0067] When the optical probe is arranged to generate multiple outputsignals from a single target area, however, their signal-to-noise ratiosmay also be improved through various averaging methods, e.g., byarithmetically or geometrically averaging such multiple output signals.In addition, the filter unit may also weight-average or ensemble-averagethe foregoing output signals. Such filtering operation can be performedin an analog and/or digital mode.

[0068] The optical imaging system may also include a spline unit forsmoothing out abrupt changes or jumps in the amplitudes of adjacentportions or data points of the output signal(s). Accordingly, the splineunit may include an interpolation algorithm or equivalent circuitry orsoftware.

[0069] The foregoing signal analyzer and signal processor of the presentinvention are preferably arranged to operate on a substantiallyreal-time basis. For example, once the optical probe is positioned inthe first target area and the wave detector generates the first outputsignal, the signal analyzer identifies the portions of the first outputsignal having similar amplitudes and the signal processor provides theself-calibrated first output signal before the optical probe is moved toor repositioned in the adjacent target area. The image processor mayalso be arranged to provide requisite images before moving the opticalprobe to other target areas as well. Therefore, the optical imagingsystem of the present invention can generate the images of two- and/orthree-dimensional distribution of the chromophores or their propertieson a substantially real time basis.

[0070] The signal analyzer of the present invention may also be arrangedto identify different points or portions of the output signals usingvarious algorithms different from the one disclosed hereinabove. Forexample, instead of focusing only on amplitudes of output signals, thesignal analyzer may calculate and assess other features of the outputsignals, e.g., curvature of the output signals which may be signified bytheir first derivative values (or slopes), concaveness or convexity ofthe output signals assessed by the values of their second derivatives,number and locations of local maximums or minimums, and the like. Forexample, when the output signal shows a slight increase or decrease,identification of such point of deflection may be facilitated byanalyzing the first and/or second derivative values of the outputsignal. In addition, by considering these secondary parameters alongwith the amplitudes of the output signals, different portions orsegments may be identified along the output signal where each portion orsegment exhibits different profiles (e.g., flat, sloped, convex orconcave).

[0071] In general, portions of the output signal with a substantiallyflat profile and similar amplitudes indicate that the region of thetarget area representing such portions of the output signal ispredominantly composed of a homogeneous material such as normal tissuesand cells. To the contrary, portions of the output signal having curvedprofile and varying amplitudes generally imply that the regions of thetarget area corresponding to such portions have optical propertiesdifferent from those of the background of the medium such as the normaltissues or cells. Accordingly, such regions are more likely than not toinclude abnormal cells, although it may also be possible that theymerely reflect normal connective structure or neurovascular tissues.Identification of a demarcation between such normal and abnormal regionsmay be facilitated by analyzing the first and/or second derivatives ofthe output signal as well.

[0072] The signal analyzer of the optical imaging system of the presentinvention is arranged to identify flat (or linear) portions of theoutput signal or, conversely, the rest of the output signal, i.e.,non-flat or curved portions. As discussed above, the signal analyzer maycompare amplitudes of each point of the output signal with the thresholdamplitude or range. Alternatively, the signal analyzer may divide theoutput signal into multiple shorter segments, obtain average amplitudesfor individual segments, and compare such averages with the thresholdamplitude or range which in turn may be a local or global maximum orminimum amplitude thereof. Regardless of the nature of the thresholdvalue, however, the output signal may vary in its amplitudes in the flatas well as non-flat portions. Thus, the signal analyzer may be providedwith a secondary cut-off amplitude or a cut-off range of deviation sothat any points of the output signal not satisfying the cut-offthreshold values may not be included in the flat or non-flat portions.

[0073] In order to ensure accuracy of a baseline of the output signalobtained from a specific target area of the medium, other baselines maybe obtained from neighboring target areas and compared with the baselinefrom the specific target area. The self-calibrating optical imagingsystem of the present invention accomplishes this objective by providingalgorithms and methods for determining a composite baseline when thebaselines obtained from different target areas are not substantiallyidentical throughout the medium.

[0074]FIGS. 4A to 4C are further exemplary output signals generated bywave detectors according to the present invention, where each figurerepresents the output signal obtained from the first, second, and thirdtarget area, respectively, and where each target area is covered bymultiple scanning elements and scanning units. As shown in the figures,the output signals of FIG. 4A and 4C have different amplitudes but flatprofiles in the first and third target areas, respectively, whereas theoutput signal of FIG. 4B decreases along the axial direction in thesecond target area. When the amplitudes of the output signal of FIG. 4Aare not substantially different from those of FIG. 4C or the differencestherebetween are within a pre-selected tolerance range, the data pointsof the output signals in FIGS. 4A to 4C may be averaged to yield thebaseline of the medium. However, when such differences are notnegligible, FIGS. 4A and 4C manifest that one of the first and thirdtarget areas may be mainly comprised of the normal tissues or cells andthe output signal therefrom represents a background output signal of themedium, whereas the other of the two target areas may be composed of theabnormal tissues or cells and, thus, its output signal is skewed orbiased upward or downward due to the presence of abnormal cells, tissuesor lumps having a size enough to cover the entire first or third targetarea. In case the signal analyzer should be provided with a thresholdamplitude or range supplied by the operator, the signal analyzercompares the data points of the target areas and locates the selectedportion(s) of the output signal to be used for estimating the baseline.However, when the signal analyzer identifies the selected portionsadaptively from the output signals themselves (e.g., by identifying thelocal or global maximum or minimums and calculating the thresholdamplitudes or ranges accordingly), the signal analyzer may have todiscern which data points should be used for calculating the baseline ofthe medium. In one embodiment, the baselines may be obtained from theadjacent target areas and compared with the baseline obtained from FIGS.4A and 4C. When the region of higher (or lower) amplitudes isconstrained to one area while the region of lower (or higher) amplitudestends to surround the constrained area, the region with the lower (orhigher) amplitudes is more likely to be the background normal tissues orcells, whereas the region having higher (or lower) amplitudes is morelikely to include the abnormal tissues, cells or lumps. Alternatively,the signal analyzer may supply the operator with different amplitudevalues and allow the operator to manually select the normal and/orabnormal region.

[0075] In some cases, output signals obtained from multiple differenttarget areas may yield similar but not identical baselines. The signalanalyzer may then be arranged to obtain a composite or average baselinefrom multiple baselines and utilize that composite baseline to normalizethe output signals obtained from all target areas of the medium. Asdiscussed above, such multiple baselines may be arithmetically,geometrically, weight- or ensemble-averaged. Alternatively, the signalanalyzer may allow the operator to select a single baseline and todesignate it as the composite baseline. Alternatively, each outputsignal (or a group thereof) may be normalized by the baseline calculatedtherefrom. When the signal processor generates the self-calibratedsignals and the image processor constructs multiple local images (e.g.,one per each scanning area or target area), a composite image may bemade from multiple local images based on the individual baselines usedin each target area (or a group thereof). This embodiment proves to beadvantageous particularly when the physiological medium includes variousanatomical structures having different optical properties. For example,the self-calibrating optical imaging system may scan the brain to detectpotential or actual stroke conditions. Brain tissues and surroundingskull normally exhibit at least minimally different opticalcharacteristics, and the thickness of the skull may vary in differentparts of the brain. When the composite baseline is calculated frommultiple baselines and used to normalize the output signals measuredfrom different parts of the brain, all image pixels will have the sameextent of normalization, i.e., identical brightness-scale or color-scaleacross the entire medium. Although such images with the uniformbackground level may assist a physician in making a comparativediagnosis, he or she may not be able to locate a mild stroke conditionwhen it is overshadowed in a target area that is normalized by abaseline having a higher amplitude. To the contrary, when the images areconstructed from the self-calibrated output signals based on individualbaselines, each target area may have its own brightness-scale orcolor-scale. Thus, the mild stroke condition may not necessarily becompromised in the image but the physician may have to analyze eachimage separately. One way of obviating such inconvenience is toartificially enhance the contrast between the background anatomicalstructure and abnormal tissues included in each target area. Forexample, upon identifying any possible abnormalities, the imaging membermay identify the demarcation line and augment the signals correspondingto the demarcation line and/or the abnormalities such that the amplifiedsignals will not be overshadowed by the color-scale or brightness-scaleof the images based on the composite baseline. A special marker or colormay also be added to such enhanced signal to alarm the physician aswell.

[0076] It is appreciated that the foregoing arrangement of the opticalimaging system of the present invention may be modified withoutdeparting from the scope of the invention. For example, the foregoingfunctional units of the signal analyzer, the signal processor, and theimage processor may be further differentiated or combined or may beimplemented into another portion of the optical imaging system. Suchfunctional units may also be arranged to form different operationalconnection therebetween. For example, the receiving unit and samplingunit of the signal analyzer may be combined. Similarly, the comparisonunit and selection unit of the signal analyzer may also be combined. Theimage processor may be arranged to operationally communicate with suchunits of the signal analyzer as well.

[0077] The foregoing self-calibrating optical imaging systems andmethods of the present invention may also be used to provide temporalchanges in blood or fluid volume in the target area of the medium. Asdiscussed in the co-pending application entitled “Optical Imaging Systemwith Movable Scanning Unit,” the concentrations of the oxygenated anddeoxygenated hemoglobins are calculated according to one of thealgorithms disclosed in the co-pending '972 application. Once suchconcentrations are obtained, their sum (i.e., total hemoglobinconcentration) is also obtained. By sampling the output signals from thewave detectors positioned in the target area over time, changes in thetotal hemoglobin concentration is obtained. By assuming that bloodhematocrit (i.e., the volume percentage of the red blood cells in blood)is maintained constant over time for blood flowing through the targetarea, temporal changes in the blood volume in such target area may bedirectly calculated in terms of temporal changes of hematocrit of thetarget area. In such cases, the optical imaging system may calculate thebaseline of the output signal and provide the self-calibrated outputsignal as discussed above. Alternatively, the optical imaging system mayalso calculate multiple baselines from the same target area over time,obtain a temporally-averaged composite baseline, and provide atemporally-compensated self-calibrated output signal.

[0078] Although the foregoing disclosure of the present invention ismainly directed to self-calibration of optical imaging systems forproviding images of the spatial distribution of the chromophoreproperty, the present invention may also be applied to optical imagingsystems for generating the images of temporal distribution thereof. Forexample, the optical probe may be arranged to scan a specific targetarea over time. From the variations in the output signals detected overdifferent intervals in the target area, the signal analyzer andprocessor can establish the baseline and provide the self-calibratedfirst output signals over time. The image processor then constructsframes of images representing temporal changes in the chromophoreproperty of the target area. Alternatively, the optical imaging systemcan also provide temporally-averaged baseline and temporally-compensatedself-calibrated output signal as described in the foregoing paragraph.It is noted that the temporal changes of the chromophore propertiesusually relate to the relative values and, thus, do not directly provideany absolute values thereof. However, once an absolute value of suchproperty is determined at any reference time frame, preceding orsubsequent changes of such property may readily be converted to theabsolute values by successively calculating the absolute valuesforwardly or backwardly.

[0079] The self-calibrating arrangements and methods of the presentinvention may be used in optical imaging systems for obtaining images ofthree-dimensional distribution of the chromophore in the physiologicalmedium. As discussed above, electromagnetic waves irradiated by the wavesource are traveling through a target volume defined by a target areaand by a pre-selected depth or thickness of the medium. Therefore, thewave detectors can generate multiple output signals each carryingoptical information of a specific target layer of the medium. Once suchoutput signals are obtained, a baseline can be estimated by theforegoing algorithms described herein. For example, a single baselinecan be designated to the entire target volume. In the alterative,multiple baselines maybe preferably defined at each depths or layers ofthe target volume. In case multiple baselines should be used, thesebaselines may be averaged or normalized with respect to each other sothat resulting three-dimensional images may be constructed under auniform gray-scale or color-grade.

[0080] Though any analytical or numerical schemes may be used to obtainsolutions of the wave equations, an exemplary algorithm unit of theinvention preferably incorporates solution schemes disclosed in theco-pending '972 application. For example, the absolute values ofconcentration of deoxygenated hemoglobin, [Hb], concentration ofoxygenated hemoglobin, [HbO], and oxygen saturation, SO₂, are obtainedby equations (8 a) to (8 d) and (9 b) of the co-pending '972application, respectively. In the alternative, the algorithm unit mayalso employ the over-determined iterative method as disclosed in theforegoing '972 application, where the absolute values of [Hb], [HbO],and SO₂ are determined by equations (17 a) to (17 c) of the co-pending'972 application, respectively. In yet another alternative, changes inthe chromophore properties are determined by estimating changes inoptical characteristics of the target area of the medium. For example,changes in concentrations of oxygenated and deoxygenated hemoglobins maybe calculated from the differences in their extinction coefficientswhich are in turn measured by electromagnetic waves having two differentwavelengths. In an exemplary numerical scheme, the photon diffusionequations are modified based on the diffusion approximation describedin, e.g., Keijer et al., “Optical Diffusion in Layered Media,” AppliedOptics, 27, p.1820-1824 (1988), and Haskell et al., “boundary Conditionsfor Diffusion Equation in Radiative Transfer,” Journal of OpticalSociety of America, A, 11, p.2727-2741, 1994. Details of the foregoingscheme is also provided in the co-pending '972 application. In each ofthese schemes, the output signals are calibrated by their baselinesobtained by one of the foregoing methods.

[0081] The wave sources and detectors of the optical probe of theoptical imaging system of the present invention may be arranged tosatisfy an embodiment disclosed in the co-pending '972 application,i.e., the wave sources and detectors are arranged to have substantiallyidentical near- and far-distances therebetween. For example, in scanningunits 125 a, 125 b of FIGS. 1A and 1B, a first near-distance between afirst wave source and a first wave detector is substantially identicalto a second near-distance between a second wave source and a second wavedetector. In addition, a first far-distance between the first wavesource and the second wave detector is substantially identical to asecond far-distance between the second wave source and a first wavedetector. A major advantage of such symmetric arrangement is thatelectromagnetic waves irradiated by the wave sources are substantiallyuniformly transmitted, absorbed, and/or scattered throughout the entirearea or volume of the medium scanned by the scanning unit. Accordingly,such scanning unit can provide uniform coverage of the target area ofthe medium and, therefore, enhance accuracy and reliability of theoutput signal (e.g., an improved signal-to-noise ratio) generated by thewave detector.

[0082] The foregoing self-calibrating optical imaging systems, opticalprobes, and methods of the present invention can be used in bothnon-invasive and invasive procedures. For example, the foregoingself-calibrating optical probes may be non-invasively disposed on thetarget area on an external surface of the test subject. Alternatively, aminiaturized self-calibrating optical probe may be implemented in a tipof a catheter which is invasively disposed on an internal target area ofthe subject. The foregoing optical imaging systems and optical probesmay also be used to determine intensive properties of the chromophoressuch as concentrations, sums of or differences in concentrations, and/orratios thereof. The foregoing optical imaging systems and probes mayfurther be utilized to calculate extensive chromophore properties suchas volume, mass, volume, volumetric flow rate or mass flow rate. Asdiscussed above, such chromophores may include, e.g., solvents of themedium, solutes dissolved in the medium, and/or other substancesincluded in the medium, each of which interacts with electromagneticwaves transmitted through the medium. Examples of the chromophores mayinclude, but not limited to, cytochromes, hormones, enzymes, both neuro-and chemo-transmitters, proteins, cholesterols, apoproteins, lipids,carbohydrates, cytosomes, blood cells, cytosols, oxyygenated hemoglobin,deoxygenated hemoglobin, and water. Specific examples of the chromophoreproperties may include, but not limited to, concentrations of oxygenatedand deoxygenated hemoglobins, oxygen saturation, and blood volume.

[0083] It is appreciated that the foregoing optical imaging systems,optical probes thereof, and methods therefor may be readily adjusted toprovide images of distribution of different chromophores or propertiesthereof. Because different chromophores generally respond toelectromagnetic waves having different wavelengths, the wave sources ofsuch optical imaging systems and probes may be manipulated to irradiateelectromagnetic waves interacting with pre-selected chromophores. Forexample, the near-infrared waves having wavelengths between 600 nm and1,000 nm, e.g., about 690 nm and 830 nm are suitable to measure thedistribution pattern of the hemoglobins and their property. However, thenear-infrared waves having wavelengths between 800 nm and 1,000 nm,e.g., about 900 nm, can also be used to measure the distribution patternof water in the medium. Selection of an optimal wavelength for detectinga particular chromophore generally depends on optical absorption and/orscattering properties of the chromophore, operational characteristics ofthe wave sources and/or detectors, and the like.

[0084] The foregoing optical imaging systems, optical probes, andmethods of the present invention may be clinically applied to detecttumors or stroke conditions in human breasts, brains, and any otherareas of the human body where the foregoing optical imaging methods suchas diffuse optical tomography is applicable. The foregoing opticalimaging systems and methods may also be applied to assess blood flowinto and out of transplanted organs or extremities and/or autografted orallografted body parts or tissues. The foregoing optical imaging systemsand methods may be arranged to substitute, e.g., ultrasonogram, X-rays,EEG, and laser-acoustic diagnostic. Furthermore, such optical imagingsystems and methods may be modified to be applicable to variousphysiological media with complicated photon diffusion and/or withnon-flat external surface.

[0085] It is noted that the optical imaging systems, optical probes, andmethods of the present invention may incorporate and/or applied torelated inventions and embodiments thereof disclosed in the commonlyassigned co-pending U.S. application Ser. No. (N/A), entitled “OpticalImaging System with Movable Scanning Unit,” another commonly assignedco-pending U.S. application Ser. No. (N/A), entitled “Optical ImagingSystem for Direct Image Construction,” and yet another commonly assignedco-pending U.S. application Ser. No. (N/A), “Optical Imaging System withSymmetric Optical Probe,” all of which have been filed on Feb. 6, 2001and all of which are incorporated herein in their entirety by reference.

[0086] Following example describes an exemplary optical imaging system,optical probe, and methods thereof according to the present invention.The results indicated that the foregoing exemplary optical imagingsystem provided reliable and accurate images of two-dimensionaldistribution of the blood volume and the oxygen saturation in the targetareas of the human breast tissues.

EXAMPLE

[0087] An exemplary optical imaging system 500 was constructed to obtainimages of two-dimensional distribution of blood volume and oxygensaturation in target areas of female human breasts. FIG. 5 is aschematic diagram of a prototype optical imaging system according to thepresent invention.

[0088] Prototype optical imaging system 500 typically included a handle501 and a main housing 505. Handle 501 was made of poly-vinylchloride(PVC) and acrylic stock, and provided with two control switches 503 a,503 b for controlling operations of various components of system 500.Main housing 505 included a body 510, a movable member 520, an actuatormember 530, an imaging member (not shown), and a pair of guiding tracks560.

[0089] Body 510 was shaped as a substantially square block(3.075″×2.8″×2.63″) and provided with barriers along its sides. Body 510was arranged to movably couple with rectangular movable member 520(1.5″×2.8″×1.05″) designed to linearly translate along a pathsubstantially parallel with one side of body 510.

[0090] Movable member 520 included two wave sources 522, S₁ and S₂, eachof which was capable of irradiating electromagnetic waves havingdifferent wavelengths. In particular, each wave source 522 included twolaser diodes, HL8325G and HL6738MG (ThorLabs, Inc., Newton, N.J.), whereeach laser diode irradiated the electromagnetic waves with wavelengthsof 690 nm and 830 nm, respectively. Movable member 520 also includedfour identical wave detectors 524 such as photo-diodes D₁, D₂, D₃, andD₄, (OPT202, Burr-Brown, Tucson, Ariz.) which were interposedsubstantially linearly between wave sources 522. Wave sources 522 anddetectors 524 were spaced at identical distances such that the foregoingsensors 522, 524 satisfy the foregoing symmetry requirements of theco-pending '972 application.

[0091] Actuator member 530 included a high-resolutionlinear-actuating-type stepper motor (Model 26000, Haydon Switch andInstrument, Inc., Waterbury, CT) and a motor controller (Spectrum PN42103, Haydon Switch and Instrument, Inc.). Actuator member 530 wasmounted on body 510 and engaged with movable member 520 so as tolinearly translate movable member 520 along guiding tracks 560 fixedlypositioned along the linear path. A pair of precision guides (Model6725K11, McMaster-Carr Supply, Santa Fe Springs, Calif.) was used asguiding tracks 560.

[0092] The imaging member was provided inside handle 501 and included adata acquisition card (DAQCARD 1200, National Instruments, Austin,Tex.). Main housing 505 was made of acrylic stocks and constructed toopen at its front face. Perspex Non-Glare Acrylic Sheet (Liard Plastics,Santa Clara, Calif.) was installed on a front face 506 of housing 505and used as a protective screen to protect wave sources 522 anddetectors 524 from mechanical damages.

[0093] In operation, movable member 520 was positioned in its startingposition, i.e., the far-left side of body 505. An operator turned on themain power of system 500 and tuned wave sources 522 and detectors 524 byrunning scanning system software. A breast of a human subject wasprepped and body 505 was positioned on the breast so that sensors 522,524 of movable member 520 were placed in a first target area of thebreast and formed appropriate optical coupling therewith. The firsttarget area was scanned by clicking one control switch 503 a on handle501. Actuator member 530 translated movable member 520 linearly alongone side of body 510 along guide tracks 560.

[0094] Wave sources 522 were synchronized to ignite their laser diodesin a pre-selected sequence. For example, a first laser diode of the wavesource, S₁, was arranged to irradiate electromagnetic waves ofwavelength 690 nm and wave detectors 524 detected the waves andgenerated a first set of output signals in response thereto. During theforegoing irradiation and detection period which generally lasted about1 msec (with duty cycle from 1:10 to 1:1,000), all other laser diodeswere turned off to minimize interference noises. After completing theirradiation and detection, the first laser diode of the wave source, S₁,was turned off and the first laser diode of the wave source, S₂, wasturned on to irradiate electromagnetic waves of the same wavelength, 690nm. Wave detectors 524 detected the waves and generated a second set ofoutput signals accordingly. Other laser diodes were maintained at offpositions during the foregoing irradiation and detection period as well.Similar procedures were repeated to the second laser diodes of the wavesources, S₁ and S₂, where both second laser diodes were arranged tosequentially irradiate the electromagnetic waves having wavelengths 830nm.

[0095] The imaging member was also synchronized with wave sources 522and detectors 524 and sampled the foregoing sets of output signals in apre-selected sampling rate. In particular, the imaging member wasarranged to process such output signals by defining a first and secondscanning units, where the first scanning unit was comprised of the wavesources, S₁ and S₂, and the wave detectors, D₁ and D₄, and the secondscanning unit was made up of the wave sources, S₁ and S₂, and the wavedetectors, D₂ and D₃. Both of the first and second scanning units hadthe source-detector arrangement which satisfied the symmetryrequirements of the co-pending '972 application. Therefore,concentrations of the oxygenated and deoxygenated hemoglobins wereobtained by the equations (1 a) to (1 e), and the oxygen saturation,SO₂, by the equation (1 e). Furthermore, relative values of blood volume(i.e., temporal changes thereof) was calculated by assessing the changesin hematocrit in the target areas as discussed above.

[0096] Actuator member 530 was also synchronized with the foregoingirradiation and detection procedures so that wave sources 522 anddetectors 524 scanned the entire target area (i.e., irradiatingelectromagnetic waves thereinto, detecting such therefrom, andgenerating the output signals) before they were moved to the nextadjacent region of the target area by actuator member 530. When movablemember 520 reached the opposing end of body 510, actuator member 530translated movable member 520 linearly to its starting position. Theforegoing irradiation and detection procedures were repeated during suchbackward linear movement of movable member 520 as well. After thescanning procedure was completed, the operator pushed the other controlswitch 503 b to send a signal to the imaging member which started imageconstruction process and provided two-dimensional images of spatialdistribution of the oxygen saturation in the target area and thetemporal changes in the blood volume therein.

[0097]FIGS. 6A and 6B are two-dimensional images of blood volume innormal and abnormal breast tissues, respectively, both measured by theoptical imaging system of FIG. 5. In addition, FIGS. 7A and 7B aretwo-dimensional images of oxygen saturation in normal and abnormalbreast tissues, respectively, both measured by the optical imagingsystem of FIG. 5 according to the present invention. As shown in thefigures, the optical imaging system provided that normal tissues had thehigher oxygen saturation (e.g., over 70%) in the area with the maximumblood volume. However, the higher oxygen saturation in the correspondingarea of the abnormal tissues was as low as 60%.

[0098] It is to be understood that, while various embodiments of theinvention has been described in conjunction with the detaileddescription thereof, the foregoing is only intended to illustrate andnot to limit the scope of the invention, which is defined by the scopeof the appended claims. Other related embodiments, aspects, advantages,and/or modifications are within the scope of the following claims.

What is claimed is:
 1. An optical imaging system for generating imagesof target areas of a physiological medium, said images representingdistribution of hemoglobins in said target areas, said systemcomprising: an optical probe having a wave source and a wave detector,wherein said wave source is configured to irradiate near-infraredelectromagnetic waves into a first target area of said physiologicalmedium and wherein said wave detector is configured to detect saidnear-infrared electromagnetic waves from said first target area of saidmedium and to generate a first output signal in response thereto; asignal analyzer configured to receive said first output signal, toanalyze amplitudes of said first output signal, and to select aplurality of points of said first output signal having substantiallysimilar amplitudes; and a signal processor configured to calculate afirst baseline from said first output signal and to provide aself-calibrated first output signal by manipulating both of said firstoutput signal and its first baseline, wherein said first baseline is arepresentative amplitude of said similar amplitudes.
 2. The system ofclaim 1 wherein said optical probe includes a two or more wave sourcesand two or more wave detectors and defines a scanning area therearound,which scanning area is a substantial portion of said first target area.3. The system of claim 1 wherein said optical probe includes two or morewave sources and two or more wave detectors and defines a scanning unitforming a scanning area therearound, which is a fraction of said firsttarget area.
 4. The system of claim 3 wherein said optical probe has anactuator and a housing, said actuator configured to move at least one ofsaid wave source and detector across a plurality of regions of saidfirst target area while said housing of said optical probe is positionedin said first target area.
 5. The system of claim 4 wherein at least oneof said wave detectors is configured to generate a plurality of saidfirst output signals in said regions of said first target area.
 6. Thesystem of claim 1 wherein said signal processor is configured to providesaid self-calibrated first output signal on a substantially real-timebasis.
 7. The system of claim 1 further comprising: an image processorconfigured to construct said images of said distribution of hemoglobinsin said first target area from said self-calibrated first outputsignals.
 8. The system of claim 7 wherein said image processor isconfigured to construct said images on a substantially real-time basis.9. The system of claim 7 wherein said hemoglobins in said first targetarea are at least one of oxygenated hemoglobin and deoxygenatedhemoglobin.
 10. The system of claim 7 wherein said images relate to saiddistribution of at least one of oxygen saturation, concentration ofoxygenated hemoglobin, concentration of deoxygenated hemoglobin, bloodvolume, and changes in blood volume in said first target area, whereinsaid oxygen saturation is defined as a ratio of said concentration ofoxygenated hemoglobin to a sum of said concentrations of oxygenated anddeoxygenated hemoglobins.
 11. The system of claim 1 wherein saiddistribution includes at least one of spatial distribution ofhemoglobins in said first target area and temporal changes in saiddistribution of hemoglobins in said first target area over time.
 12. Thesystem of claim 1 further comprising: a memory unit configured to storeat least one of said first output signal, first baseline, andself-calibrated first output signal.
 13. The system of claim 1 whereinsaid signal analyzer includes: a threshold unit for providing athreshold amplitude; a comparison unit for comparing said amplitudes ofsaid first output signal with said threshold amplitude; and a selectionunit for identifying said plurality of said points of said first outputsignal having substantially similar amplitudes.
 14. The system of claim13 wherein said threshold unit is configured to receive said thresholdamplitude from an operator.
 15. The system of claim 13 wherein saidthreshold unit is configured to calculate a reference amplitude fromsaid first output signal and to calculate said threshold amplitude fromsaid reference amplitude.
 16. The system of claim 15 wherein saidreference amplitude is calculated from at least one of: a local maximumof said first output signal from said first target area; a local minimumof said first output signal from said first target area; an average ofat least a portion of said first output signal; a global maximum of aplurality of said output signals from a plurality of said target areasof said medium; a global minimum of a plurality of said output signalsfrom a plurality of said target areas of said medium; and a combinationthereof.
 17. The system of claim 15 wherein said threshold amplitude isa product of said reference amplitude and a pre-determined factor. 18.The system of claim 13 wherein said similar amplitudes of said pluralityof said points are one of those greater than said threshold amplitudeand those less than said threshold amplitude.
 19. The system of claim 1wherein said signal analyzer includes: a threshold unit for providing athreshold range of said amplitudes; a comparison unit for comparing saidamplitudes of said first output signal with said threshold range; and aselection unit for identifying said plurality of said points of saidfirst output signal.
 20. The system of claim 19 wherein said similaramplitudes of said plurality of said points are one of those fallingwithin said threshold range and those falling outside said thresholdrange.
 21. The system of claim 1 wherein said signal processor includesan averaging unit for calculating said first baseline as an average ofsaid similar amplitudes, wherein said average is one of: an arithmeticaverage of said similar amplitudes; a geometric average of said similaramplitudes; a weight-average of said similar amplitudes; and anensemble-average of said similar amplitudes.
 22. The system of claim 1wherein said signal processor includes a calibration unit for providingsaid self-calibrated first output signal by normalizing said firstoutput signal by said first baseline thereof.
 23. The system of claim 22wherein said self-calibrated first output signal is one of: a ratio ofsaid first output signal to its first baseline; and a ratio of adifference between said first output signal and its first baseline tosaid first baseline.
 24. The system of claim 1 wherein said signalanalyzer includes at least one filter unit configured to improvesignal-to-noise ratio of said first output signal.
 25. The system ofclaim 24 wherein said filter unit includes at least one of: an averagingunit configured to provide at least one of an arithmetic average,geometric average, ensemble-average, and weight-average of a pluralityof said first output signals from said first target area; and a low passfilter configured to remove high frequency noise from said first outputsignal.
 26. The system of claim 1 wherein said signal analyzer furtherincludes a control unit configured to store a plurality of saidbaselines measured in a plurality of target areas of said medium and tocompare at least one of said baselines with the others thereof.
 27. Thesystem of claim 26 wherein said control unit is configured to provide anaverage of said plurality of said baselines.
 28. The system of claim 26wherein said control unit is configured to generate a signal when atleast one of said baselines is at least substantially different from atleast one of the others thereof.
 29. An optical imaging systemconfigured to generate images of target areas of a physiological medium,said images representing distribution of chromophores or propertiesthereof in said target areas, said system including at least one wavesource configured to irradiate electromagnetic waves into said mediumand at least one wave detector configured to detect electromagneticwaves from said medium and to generate output signal in responsethereto, said system comprising: a signal analyzer configured to receivea first output signal from said wave detector, to analyze amplitudes ofsaid first output signal, and to select a plurality of points of saidfirst output signal having substantially similar amplitudes, whereinsaid first output signal is representative of said distribution in afirst target area of said medium; a signal processor configured tocalculate a first baseline predominantly from said first output signaland to provide a self-calibrated first output signal by manipulatingboth of said first output signal and its first baseline, where saidfirst baseline corresponds to a representative amplitude of said similaramplitudes; and an image processor configured to construct said imagesof said distribution of at least one of said chromophores and saidproperties thereof from said self-calibrated first output signal.
 30. Anoptical imaging system configured to generate images of target areas ofa physiological medium, said images representing distribution ofchromophores or properties thereof in said target areas, said systemincluding at least one wave source configured to irradiateelectromagnetic waves into said medium and at least one wave detectorconfigured to detect electromagnetic waves from said medium and togenerate output signal in response thereto, said system comprising: amovable member including at least one of said wave source and detector,said wave detector configured to generate a first output signal from afirst target area of said medium, wherein said first output signal isrepresentative of said distribution in a first target area of saidmedium; an actuator member configured to generate at least one movementof said movable member; a signal analyzer configured to receive saidfirst output signal, to analyze amplitudes of said first output signal,and to select a plurality of points of said first output signal havingsubstantially similar amplitudes; a signal processor configured tocalculate a first baseline predominantly from said first output signaland to provide a self-calibrated first output signal by manipulatingboth of said first output signal and its first baseline, wherein saidfirst baseline corresponds to a representative amplitude of said similaramplitudes; and an image processor configured to construct said imagesof said distribution of at least one of said chromophores and saidproperties thereof from said self-calibrated first output signal.
 31. Anoptical imaging system configured to generate images of target areas ofa physiological medium, said images representing distribution of one ofchromophores and their properties in said target areas, said systemcomprising: an optical probe having at least wave source and at leastone wave detector, wherein said wave source is configured to irradiateelectromagnetic waves into a first target area of said physiologicalmedium and wherein said wave detector is configured to detect saidelectromagnetic waves from said first target area of said medium and togenerate a first output signal in response thereto; a signal analyzerwhich is configured to receive said first output signal, to analyzeamplitudes of said first output signal, and to select a plurality ofpoints of said first output signal having substantially similaramplitudes; and a signal processor which is configured to calculate afirst baseline from said first output signal and to provide aself-calibrated first output signal by manipulating both of said firstoutput signal and its first baseline, wherein said first baseline is arepresentative amplitude of said similar amplitudes.
 32. A method forobtaining a calibrated output signal from an optical imaging systemhaving an optical probe with at least one wave source configured toirradiate near-infrared electromagnetic waves into target areas of aphysiological medium and at least one wave detector configured togenerate output signal in response to said near-infrared electromagneticwaves detected thereby, the method comprising: positioning said opticalprobe on a first target area of said medium; generating a first outputsignal without displacing said optical probe from said first targetarea; identifying at least one first portion of said first outputsignal, wherein the signal in said first portion has substantiallysimilar first amplitudes; and obtaining a first baseline of said firstoutput signal as a representative value of said substantially similarfirst amplitudes.
 33. The method of claim 32 further comprising:normalizing said first output signal by said first baseline to provide aself-calibrated first output signal.
 34. The method of claim 33 whereinsaid normalizing step comprises: providing a ratio signal representing aratio of said first output signal to its first baseline.
 35. The methodof claim 33 wherein said normalizing step comprises: providing adifference signal representing a difference between said first outputsignal and its first baseline; and providing a ratio signal representinga ratio of said difference signal to said first baseline of said firstoutput signal.
 36. The method of claim 32 wherein said generating stepcomprises: providing movement of at least one of said wave source anddetector over said first target area; and generating said first outputsignal during said movement.
 37. The method of claim 32 furthercomprising: reducing noise from said first output signal prior toperforming at least one of said identifying and obtaining steps.
 38. Themethod of claim 37 wherein said reducing step comprises at least one of:arithmetically averaging a plurality said first output signals;geometrically averaging a plurality of said first output signals;weight-averaging a plurality of said first output signals;ensemble-averaging a plurality of said first output signals; andprocessing at least a portion of said first output signal through alow-pass filter.
 39. The method of claim 32 wherein said identifyingstep comprises one of: selecting a threshold amplitude and identifyingsaid first portion having said amplitudes greater than said thresholdamplitude; selecting a threshold amplitude and identifying said firstportion having said amplitudes less than said threshold amplitude;selecting at least one threshold range and identifying said firstportion having said amplitudes falling within said threshold range; andselecting at least one threshold range and identifying said firstportion having said amplitudes falling outside said threshold range. 40.The method of claim 39 wherein said selecting step comprises one of:manually selecting at least one of said threshold amplitude and range;and providing a reference amplitude and providing at least one of saidthreshold amplitude and range based on said reference amplitude.
 41. Themethod of claim 40 wherein said reference amplitude is one of: a localmaximum of said first output signal from said first target area; a localminimum of said first output signal from said first target area; anaverage of at least one portion of said first output signal; a globalmaximum of a plurality of said output signals from a plurality of saidtarget areas of said medium; a global minimum of a plurality of saidoutput signals from a plurality of said target areas of said medium; andand a combination thereof.
 42. The method of claim 40 wherein saidproviding step comprises: multiplying said reference amplitude by apre-selected factor to provide at least one of said threshold amplitudeand range.
 43. The method of claim 32 wherein said obtaining stepcomprises one of: arithmetically averaging said similar amplitudes;geometrically averaging said similar amplitudes; and weight-averagingsaid similar amplitudes.
 44. The method of claim 32 further comprising:displacing said optical probe to a second target area of said medium;generating a second output signal from said second target area; andnormalizing said second output signal by said first baseline of saidfirst target area to provide a self-calibrated second output signal. 45.The method of claim 44 further comprising: repeating said displacing andgenerating steps of claim 43 in a plurality of said target areas of saidmedium.
 46. The method of claim 32 further comprising: displacing saidoptical probe to a second target area of said medium; generating asecond output signal from said second target area; identifying at leastone second portion of said second output signal, wherein said secondportion has substantially similar second amplitudes; and obtaining asecond baseline of said second output signal as a representative valueof said substantially similar second amplitudes.
 47. The method of claim46 further comprising: calculating a composite baseline by averagingsaid first baseline from said first target area and said second baselinefrom said second target area; and normalizing said first and secondoutput signals by said composite baseline.
 48. The method of claim 47wherein said calculating step comprises one of: arithmetically averagingsaid baselines; weight-averaging said baselines; and selecting one ofsaid baselines as said composite baseline.
 49. A method for obtaining acalibrated output signal from an optical imaging system including anoptical probe with at least one wave source and at least one wavedetector, said wave source configured to irradiate near-infraredelectromagnetic waves into target areas of a physiological medium whichincludes a normal region and an abnormal region, said wave detectorconfigured to generate output signal in response to said near-infraredelectromagnetic waves detected thereby, said method comprising:positioning said optical probe on a first target area of said medium;generating a first output signal without displacing said optical probefrom said first target area; identifying at least one first portion ofsaid first output signal attributed to said normal region of said targetarea; and obtaining a first baseline of said first output signal from arepresentative value of said first portion of said first output signal,wherein said first portion attributed to said normal region ischaracterized by substantially flat profile and by substantially similarfirst amplitudes.
 50. A method for calibrating an optical imaging systemhaving an optical probe with at least one wave source for irradiatingnear-infrared electromagnetic waves into target areas of a physiologicalmedium and at least one wave detector for generating output signals inresponse to near-infrared electromagnetic waves detected thereby, saidmethod comprising: positioning said optical probe on a first target areaof said medium; generating a first output signal without displacing saidoptical probe from said first target area; identifying at least onefirst portion of said first output signal having substantially similarfirst amplitudes before displacing said optical probe from said firsttarget area; and obtaining a first baseline of said first output signalfrom a representative value of said substantially similar amplitudesbefore displacing said optical probe from said first target area. 51.The method of claim 50 further comprising: normalizing said first outputsignal by said first baseline to provide a self-calibrated first outputsignal on a substantially real time basis.
 52. The method of claim 51further comprising: generating at least one of images of said firstoutput signal, images of said self-calibrated first output signal,images based on said first output signal, and images based on saidself-calibrated first output signal.